disease_class n percent
Control 137 7.71%
SLE 1640 92.29%

Differential Gene Expression

comparison up up % down down % mean count cutoff low counts low counts %
SLE vs Control 6628 13.34 % 5091 10.25 % 0 19195 38.63 %
Note:
49690 with nonzero total read count
Outliers: 0

25 genes with largest negative log-fold change in experimental group

SLE_vs_Control: downregulated in SLE
gene log2FoldChange lfc standard error pvalue* padj
DDX3Y 4.7 0.40 0.0e+00 1.9e-23
MT-RNR2 4.6 0.23 0.0e+00 2.2e-08
HBB 4.3 0.22 2.0e-04 0.00094
MT-RNR1 4.3 0.22 0.0e+00 4.6e-11
TXLNGY 4.3 0.30 0.0e+00 6.8e-42
EIF1AY 4.0 0.55 2.6e-04 0.0012
KDM5D 3.4 0.19 0.0e+00 1.7e-70
AC108065.1 3.1 0.74 5.3e-04 0.0022
RAB17 2.4 0.34 0.0e+00 1.9e-10
MTCO1P40 2.3 0.52 8.1e-04 0.0032
MTND1P23 1.9 0.54 6.1e-05 0.00033
A4GALT 1.6 0.23 0.0e+00 1.3e-11
PLD5 1.6 0.30 0.0e+00 1.7e-08
AC006065.5 1.5 0.29 1.6e-06 1.2e-05
BCORP1 1.4 0.29 6.7e-06 4.4e-05
SNORD95 1.4 0.24 0.0e+00 4.8e-09
AC007368.1 1.3 0.29 1.0e-07 1.1e-06
AP001329.1 1.3 0.26 2.5e-06 1.8e-05
SNORD13 1.3 0.17 0.0e+00 1.3e-15
SNORD33 1.3 0.19 2.6e-04 0.0012
SNORD55 1.3 0.25 0.0e+00 9.6e-08
MTND4P12 1.2 0.18 0.0e+00 4.1e-11
NOVA1 1.2 0.30 2.0e-04 0.00093
RNU6ATAC 1.2 0.18 0.0e+00 5.7e-11
SNX18P13 1.2 0.17 0.0e+00 1e-11
* Wald test p-values
Benjamini–Hochberg adjusted value

25 genes with largest positive log-fold change in experimental group

SLE_vs_Control: upregulated in SLE
gene log2FoldChange lfc standard error pvalue* padj
RN7SKP71 7.4 0.62 0.0e+00 2.4e-36
RN7SL5P 7.3 0.55 0.0e+00 3.2e-40
OTOF 4.5 0.25 0.0e+00 3.1e-73
NKAIN1 3.9 0.71 9.6e-05 0.00049
PCSK9 3.9 0.71 1.5e-05 9e-05
ADAMTS2 3.8 0.34 0.0e+00 9e-33
H3F3AP6 3.8 0.91 5.2e-03 0.016
RN7SKP203 3.8 0.45 0.0e+00 7.7e-19
PAX3 3.0 0.48 0.0e+00 4.1e-07
LINC01388 2.9 0.63 6.5e-04 0.0026
SLC8A2 2.9 0.29 7.4e-05 0.00039
IFI44L 2.8 0.18 0.0e+00 5.9e-54
Z84484.1 2.7 0.55 1.5e-04 0.00073
IFI27 2.6 0.23 0.0e+00 6.6e-28
RN7SL396P 2.6 0.53 0.0e+00 8.9e-09
SIGLEC1 2.6 0.17 0.0e+00 2.3e-50
USP18 2.6 0.16 0.0e+00 4.6e-56
AL592158.1 2.5 0.26 0.0e+00 1e-20
RSAD2 2.5 0.16 0.0e+00 8.5e-55
AC068299.2 2.4 0.19 0.0e+00 1.2e-34
HSPB9 2.4 0.61 9.1e-03 0.026
LINC00487 2.4 0.23 0.0e+00 2.7e-27
PGF 2.4 0.25 0.0e+00 6.8e-15
RN7SL713P 2.4 0.41 0.0e+00 3.2e-07
7SK 2.3 0.25 0.0e+00 4.7e-20
IFI44 2.3 0.15 0.0e+00 5.2e-53
RN7SKP176 2.3 0.87 9.0e-05 0.00046
USP41 2.3 0.27 0.0e+00 5.1e-27
* Wald test p-values
Benjamini–Hochberg adjusted value

Expression of top class DE genes by class

Expression of all top DE genes

Volcano plot of gene expression

## Warning: Removed 19374 rows containing missing values (geom_point).

Expression of selected interferon-stimulated genes

Expression of individual genes in the M1.2, M3.4, and M5.12 gene modules

Sample Clustering

Using gene expression distance, a sample adjacency matrix was calculated from a shared nearest neighbor graph. This, in turn, was used to cluster the samples, with the optimal clustering resolution being determined by silhouette width at multiple resolutions.

Clustering and variation of samples in reduced dimensional space

PCA

PCA, by disease classification

PCA, by plate

PCA, by initial sample concentration

PCA, by Leiden cluster

3D PCA, colored by Leiden cluster

UMAP

UMAP, by disease classification

UMAP, by plate

UMAP, by initial sample concentration

UMAP, by Leiden cluster

UMAP, in 3D, colored by Leiden cluster

Module scores

SLE Interferon module scores

SLE Inflammatory module scores

Low-density granulocyte module scores

SLE Modules with an annotated associated pathway

All SLE modules

Viral trancription

Samples were examined for transcripts from the following viruses: HSV-1, HSV-2, VZV, EBV, EBV-2, HCMV, HHV7, KSHV, Adenovirus 2, B19, HIV-1, HBV, HPV-2, HPV-16, JCV, and MCV-1

Detected viral transcription and Interferon module scores

Detected viral transcription and Inflammatory module scores

WGCNA

Expression similarity dendrogram

Expression of identified modules

By cluster

By disease classification

WGCNA eigenvalues

Gene ontology GSEA of WGCNA modules

Use of WGCNA modules in classifying clusters.

The module eigengene scores were used to train a random forest model with repeated cross validation to predict cluster identity.

The model was trained with 75% of the dataset and tested on 25%.

## Confusion Matrix and Statistics
## 
##           Reference
## Prediction   1   2   3
##          1 241  18   4
##          2   7 156   0
##          3   0   0   3
## 
## Overall Statistics
##                                           
##                Accuracy : 0.9324          
##                  95% CI : (0.9044, 0.9543)
##     No Information Rate : 0.5781          
##     P-Value [Acc > NIR] : < 2.2e-16       
##                                           
##                   Kappa : 0.8624          
##                                           
##  Mcnemar's Test P-Value : NA              
## 
## Statistics by Class:
## 
##                      Class: 1 Class: 2 Class: 3
## Sensitivity            0.9718   0.8966 0.428571
## Specificity            0.8785   0.9725 1.000000
## Pos Pred Value         0.9163   0.9571 1.000000
## Neg Pred Value         0.9578   0.9323 0.990610
## Prevalence             0.5781   0.4056 0.016317
## Detection Rate         0.5618   0.3636 0.006993
## Detection Prevalence   0.6131   0.3800 0.006993
## Balanced Accuracy      0.9251   0.9346 0.714286

The relative importance of each eigengene in classification:

## parRF variable importance
## 
##   variables are sorted by maximum importance across the classes
##   only 20 most important variables shown (out of 31)
## 
##                     1      2       3
## MEmagenta      28.659 29.246  6.7112
## MEtan          25.455 24.937  8.3923
## MEgrey60       17.545 22.498  0.9272
## MElightcyan    15.667 18.279 11.0346
## MEturquoise    13.192 16.259  5.4120
## MEbrown        15.646 13.757  6.5662
## MEblue         13.812 14.841  3.2210
## MEgreen        13.781 14.264  9.8092
## MEpink         12.704  8.216 11.6982
## MEskyblue       8.591 12.589  5.3575
## MEorange       12.200 12.050  0.9116
## MElightyellow  12.189  4.574  3.0055
## MEdarkred       9.118 11.943  0.6649
## MEcyan          9.559 11.696  5.4114
## MEdarkgrey     11.270  8.918  5.2972
## MEmidnightblue 10.910  6.147  2.8580
## MEpurple        8.720 10.029  4.5571
## MEdarkgreen     9.573  9.954  4.3913
## MEroyalblue     9.516  3.773  3.1790
## MEdarkorange    9.432  6.597  1.0613

Use of WGCNA modules in labeling disease class.

The module eigengene scores were used to train a random forest model with repeated cross validation to predict cluster identity.

The model was trained with 75% of the dataset and tested on 25%.

## Confusion Matrix and Statistics
## 
##           Reference
## Prediction Control SLE
##    Control      14   5
##    SLE          24 387
##                                           
##                Accuracy : 0.9326          
##                  95% CI : (0.9046, 0.9544)
##     No Information Rate : 0.9116          
##     P-Value [Acc > NIR] : 0.0703022       
##                                           
##                   Kappa : 0.4594          
##                                           
##  Mcnemar's Test P-Value : 0.0008302       
##                                           
##             Sensitivity : 0.36842         
##             Specificity : 0.98724         
##          Pos Pred Value : 0.73684         
##          Neg Pred Value : 0.94161         
##              Prevalence : 0.08837         
##          Detection Rate : 0.03256         
##    Detection Prevalence : 0.04419         
##       Balanced Accuracy : 0.67783         
##                                           
##        'Positive' Class : Control         
## 

The relative importance of each eigengene in classification:

## parRF variable importance
## 
##   only 20 most important variables shown (out of 31)
## 
##                 Overall
## MEtan            31.387
## MEgreenyellow    12.638
## MEdarkgrey        8.846
## MEcyan            8.583
## MEsteelblue       8.043
## MEpaleturquoise   6.910
## MEturquoise       6.614
## MEdarkgreen       6.330
## MEpink            5.854
## MElightcyan       5.725
## MEwhite           5.389
## MEdarkorange      5.332
## MEdarkturquoise   5.256
## MEred             4.906
## MEskyblue         4.898
## MEdarkred         4.789
## MEgrey60          4.616
## MEmagenta         4.274
## MEmidnightblue    3.817
## MEblack           3.773

Data processing of RNAseq data

Overview of sample characteristics:

## 1777 samples selected for analysis
## 1774 files found
## All files match a metadata entry.
## A count file was not found for the following selected samples:
## [1] "AA00393"   "AA00150_2" "AA03681_2"

Sample QC filtering

Samples with a PC1 > 2 (the red lines) and/or PC2 zscore > 2.5 (the green lines) were dropped from analysis.

Removing the following samples:
sample_name disease_class project run_id sample_alias sex race_code initial_concentration_ng_ul final_concentration_ng_ul rin
AA02818 Control DxTerity S4_004_1 none Female [EA] 1.518 1.518 6.1
AA02024 SLE DxTerity S4_004_1 S00898-V08157 Female [EA] 2.863 2.863 7.4
AA02588 SLE DxTerity S4_004_1 none Female [EA] 27.140 3.360 8.4
AA03427 SLE DxTerity S4_004_1 S00898-V09086 Female [EA] 14.853 14.853 7.8
AA01977 SLE DxTerity S4_004_1 S00891-V08104 Female [EA] 1.511 1.511 7.8
AA03811 SLE DxTerity S4_004_1 S00096-V09475 Female [EA] 2.775 2.775 5.1
AA03609 SLE DxTerity S4_004_1 S00909-V09268 Female [AA] 1.602 1.602 8.0
AA02925 SLE DxTerity S4_004_1 S00582-V08574 Female [EA] 6.603 6.603 5.9
AA03322 SLE DxTerity S4_004_2 S00577-V08979 Female [AA] 37.535 5.712 6.7
AA04331 SLE ABC S4_004_4 ABC-39-V-SCR Female [AA] 14.243 14.243 8.1
AA04332 SLE ABC S4_004_4 ABC-40-V-01 Female [EA] 2.824 2.824 9.8
AA04358 SLE ABC S4_004_4 ABC-54-V-SCR Female [EA] 4.479 4.479 10.0
AA04365 SLE ABC S4_004_4 ABC-57-V-01 Male [EA] 7.621 7.621 9.8
AA04370 SLE ABC S4_004_4 ABC-57-V-07 Male [EA] 10.127 10.127 9.6
AA04444 SLE ABC S4_005_1 ABC-54-V-07 Female [EA] 7.359 7.359 7.0
AA01979 SLE DxTerity S4_005_1 S00158-V08102 Female [EA][H] 8.574 8.574 6.8
AA02257 SLE DxTerity S4_005_1 none Female [EA][H] 3.485 3.485 7.1
AA02583 SLE DxTerity S4_005_1 none Female [EA][H] 7.620 7.620 7.0
AA01979_2 SLE DxTerity S4_005_2 S00158-V08102 Female [EA][H] 7.571 7.571 6.8
AA02583_2 SLE DxTerity S4_005_2 none Female [EA][H] 7.870 7.870 7.0
AA04567 SLE ABC S4_006_1 ABC-54-V-05 Female [EA] 3.105 3.105 6.9
AA04517 SLE ABC S4_006_1 ABC-54-V-06 Female [EA] 4.136 4.136 7.9
AA04584 SLE DxTerity S4_006_2 S00211-V07644 Male [EA] 5.920 5.920 NA
AA00722 SLE DxTerity S4_006_2 S00429-V06264 Female [A] 7.940 7.940 NA
AA02938 SLE DxTerity S4_006_2 S00627-V08586 Male [AA] 1.860 1.860 NA
AA00961 SLE DxTerity S4_006_3 S00477-V06702 Female [EA] 19.500 19.500 6.0
AA01057 SLE DxTerity S4_006_3 S00477-V06843 Female [EA] 11.300 11.300 6.3
AA01455 SLE DxTerity S4_006_3 S00675-V07447 Female [EA] 69.200 69.200 6.8
AA01842 SLE DxTerity S4_006_3 S00323-V07949 Female [EA] 29.000 29.000 6.8
AA00420 SLE DxTerity S4_006_4 S00275-V05407 Female [EA] 1.680 1.680 6.6
AA03584 SLE OCRD S4_007_1 S00052-V09246 Female [AI] 54.031 NA NA
AA03287 SLE OCRD S4_007_1 S00609-V08946 Female [EA] 8.303 NA NA
AA00816 SLE OCRD S4_007_1 S00609-V06447 Female [EA] 17.051 NA NA
AA00634 SLE OCRD S4_007_1 S00609-V06107 Female [EA] 9.655 NA NA
AA00032 SLE OCRD S4_007_3 S00158-V03597 Female [EA][H] 2.818 NA NA
AA01333 SLE OCRD S4_007_3 S00158-V07271 Female [EA][H] 3.349 NA NA
AA02944 SLE OCRD S4_007_3 S00158-V08593 Female [EA][H] 2.799 NA NA
AA01842_2 SLE OCRD S4_008_1 S00323-V07949 Female [EA] 31.474 31.474 NA
AA00555 SLE OCRD S4_008_1 S00180-V05964 Male [EA] 15.928 15.928 NA
AA04628 SLE BLAST S4_008_2 BT-01-V-SCR Female [EA] 13.851 13.851 NA
AA04629 SLE BLAST S4_008_2 BT-01-V-BSL Female [EA] 21.819 21.819 NA
AA04630 SLE BLAST S4_008_2 BT-01-V-01 Female [EA] 1.776 1.776 NA
AA04636 SLE BLAST S4_008_2 BT-01-V-05 Female [EA] 5.166 5.166 NA
AA04637 SLE BLAST S4_008_2 BT-01-V-06 Female [EA] 6.480 6.480 NA
AA04773 SLE BLAST S4_008_3 BT-17-V-07 Female [EA] 51.200 51.200 NA
AA04782 SLE BLAST S4_008_3 BT-18-V-02 Female [EA] 10.900 10.900 NA
AA04784 SLE BLAST S4_008_3 BT-20-V-SCR Female [EA] 11.400 11.400 NA
AA04873 SLE BLAST S4_008_4 BT-30-V-SCR Female [AI] 14.240 14.240 NA
AA05003 SLE OCRD S4_009_1 S00577-V10295 Female [AA] 6.755 6.755 NA
AA00901 SLE OCRD S4_009_2 S00371-V06601 Female [EA] 57.725 57.725 NA
AA01442 SLE OCRD S4_009_4 S00829-V07429 Female [EA] 71.940 71.940 NA
AA01272 SLE OCRD S4_009_4 S00750-V07189 Female [EA][H] 15.602 15.602 NA

Overall correlation between samples

Data quality

MA-plot

This MA plot is of shrunken log2 fold changes (using the apeglm package), in which actual fold changes are adjusted to compensate for the high variablity of genes with few counts.

Dots in red indicate a significant expression difference between Control and SLE.

Dispersion estimates

Cluster resolution optimization

The samples are clustered using the Leiden algorithm on shared nearest neighbors calculated from sample distances. Since the clustering resolution is an emperical value that has to be determined for each dataset, a range of resolutions were tested and then the silhouette coefficient was calculated at each resolution. A higher coefficient means better intracluster simliarity and intercluster differences.

Sample Sanity check

To determine if there is a gross mixup of samples, examine the expression of sex-specific transcripts to ensure that only female-subject samples express “XIST” and male-subject samples "DDX3Y:

These appear to be correct.

## Warning in system("timedatectl", intern = TRUE): running command 'timedatectl' had status 1
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##  version  R version 3.6.1 (2019-07-05)
##  os       Debian GNU/Linux 9 (stretch)
##  system   x86_64, linux-gnu           
##  ui       X11                         
##  language (EN)                        
##  collate  en_US.UTF-8                 
##  ctype    en_US.UTF-8                 
##  tz       Etc/UTC                     
##  date     2020-02-07                  
## 
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##  foreign                0.8-72      2019-08-02 [2] CRAN (R 3.6.1)                           
##  formattable          * 0.2.0.1     2016-08-05 [1] CRAN (R 3.6.1)                           
##  Formula                1.2-3       2018-05-03 [1] CRAN (R 3.6.1)                           
##  fs                     1.3.1       2019-05-06 [1] CRAN (R 3.6.1)                           
##  furrr                * 0.1.0       2018-05-16 [1] CRAN (R 3.6.1)                           
##  future               * 1.15.1      2019-11-25 [1] CRAN (R 3.6.1)                           
##  future.apply           1.3.0       2019-06-18 [1] CRAN (R 3.6.1)                           
##  gargle                 0.4.0       2019-10-04 [1] CRAN (R 3.6.1)                           
##  gbRd                   0.4-11      2012-10-01 [1] CRAN (R 3.6.1)                           
##  gdata                  2.18.0      2017-06-06 [1] CRAN (R 3.6.1)                           
##  genefilter             1.68.0      2019-10-29 [1] Bioconductor                             
##  geneplotter            1.64.0      2019-10-29 [1] Bioconductor                             
##  generics               0.0.2       2018-11-29 [1] CRAN (R 3.6.1)                           
##  GenomeInfoDb         * 1.22.0      2019-10-29 [1] Bioconductor                             
##  GenomeInfoDbData       1.2.2       2019-11-06 [1] Bioconductor                             
##  GenomicRanges        * 1.38.0      2019-10-29 [1] Bioconductor                             
##  ggfittext              0.8.1       2019-07-18 [1] CRAN (R 3.6.1)                           
##  ggforce              * 0.3.1       2019-08-20 [1] CRAN (R 3.6.1)                           
##  ggplot2              * 3.2.1       2019-08-10 [1] CRAN (R 3.6.1)                           
##  ggplotify              0.0.4       2019-08-06 [1] CRAN (R 3.6.1)                           
##  ggraph                 2.0.0       2019-09-02 [1] CRAN (R 3.6.1)                           
##  ggrepel              * 0.8.1       2019-05-07 [1] CRAN (R 3.6.1)                           
##  ggridges               0.5.1       2018-09-27 [1] CRAN (R 3.6.1)                           
##  globals                0.12.5      2019-12-07 [1] CRAN (R 3.6.1)                           
##  glue                   1.3.1       2019-03-12 [1] CRAN (R 3.6.1)                           
##  GO.db                  3.10.0      2020-01-05 [1] Bioconductor                             
##  googleAuthR            1.1.1       2019-09-09 [1] CRAN (R 3.6.1)                           
##  googleCloudStorageR    0.5.1       2019-08-31 [1] CRAN (R 3.6.1)                           
##  GOSemSim               2.12.0      2019-10-29 [1] Bioconductor                             
##  gower                  0.2.1       2019-05-14 [1] CRAN (R 3.6.1)                           
##  gplots                 3.0.1.1     2019-01-27 [1] CRAN (R 3.6.1)                           
##  graphlayouts           0.5.0       2019-08-20 [1] CRAN (R 3.6.1)                           
##  gridBase               0.4-7       2014-02-24 [1] CRAN (R 3.6.1)                           
##  gridExtra              2.3         2017-09-09 [1] CRAN (R 3.6.1)                           
##  gridGraphics           0.4-1       2019-05-20 [1] CRAN (R 3.6.1)                           
##  gtable                 0.3.0       2019-03-25 [1] CRAN (R 3.6.1)                           
##  gtools               * 3.8.1       2018-06-26 [1] CRAN (R 3.6.1)                           
##  haven                  2.2.0       2019-11-08 [1] CRAN (R 3.6.1)                           
##  HGNChelper           * 0.8.1       2019-10-24 [1] CRAN (R 3.6.1)                           
##  highr                  0.8         2019-03-20 [1] CRAN (R 3.6.1)                           
##  Hmisc                  4.3-0       2019-11-07 [1] CRAN (R 3.6.1)                           
##  hms                    0.5.2       2019-10-30 [1] CRAN (R 3.6.1)                           
##  htmlTable              1.13.3      2019-12-04 [1] CRAN (R 3.6.1)                           
##  htmltools              0.4.0       2019-10-04 [1] CRAN (R 3.6.1)                           
##  htmlwidgets            1.5.1       2019-10-08 [1] CRAN (R 3.6.1)                           
##  httpuv                 1.5.2       2019-09-11 [1] CRAN (R 3.6.1)                           
##  httr                   1.4.1       2019-08-05 [1] CRAN (R 3.6.1)                           
##  ica                    1.0-2       2018-05-24 [1] CRAN (R 3.6.1)                           
##  igraph                 1.2.4.2     2019-11-27 [1] CRAN (R 3.6.1)                           
##  import                 1.1.0       2015-06-22 [1] CRAN (R 3.6.1)                           
##  impute                 1.60.0      2019-10-29 [1] Bioconductor                             
##  inspectdf              0.0.7       2019-11-05 [1] CRAN (R 3.6.1)                           
##  ipred                  0.9-9       2019-04-28 [1] CRAN (R 3.6.1)                           
##  IRanges              * 2.20.1      2019-11-20 [1] Bioconductor                             
##  irlba                  2.3.3       2019-02-05 [1] CRAN (R 3.6.1)                           
##  iterators              1.0.12      2019-07-26 [1] CRAN (R 3.6.1)                           
##  janitor              * 1.2.0       2019-04-21 [1] CRAN (R 3.6.1)                           
##  jcolors                0.0.4       2019-05-22 [1] CRAN (R 3.6.1)                           
##  jpeg                   0.1-8.1     2019-10-24 [1] CRAN (R 3.6.1)                           
##  jsonlite               1.6         2018-12-07 [1] CRAN (R 3.6.1)                           
##  kableExtra           * 1.1.0       2019-03-16 [1] CRAN (R 3.6.1)                           
##  KernSmooth             2.23-16     2019-10-15 [2] CRAN (R 3.6.1)                           
##  knitr                  1.26        2019-11-12 [1] CRAN (R 3.6.1)                           
##  labeling               0.3         2014-08-23 [1] CRAN (R 3.6.1)                           
##  later                  1.0.0       2019-10-04 [1] CRAN (R 3.6.1)                           
##  lattice              * 0.20-38     2018-11-04 [2] CRAN (R 3.6.1)                           
##  latticeExtra           0.6-29      2019-12-19 [1] CRAN (R 3.6.1)                           
##  lava                   1.6.6       2019-08-01 [1] CRAN (R 3.6.1)                           
##  lazyeval               0.2.2       2019-03-15 [1] CRAN (R 3.6.1)                           
##  leiden               * 0.3.1       2019-07-23 [1] CRAN (R 3.6.1)                           
##  lifecycle              0.1.0       2019-08-01 [1] CRAN (R 3.6.1)                           
##  listenv                0.8.0       2019-12-05 [1] CRAN (R 3.6.1)                           
##  lmtest                 0.9-37      2019-04-30 [1] CRAN (R 3.6.1)                           
##  locfit                 1.5-9.1     2013-04-20 [1] CRAN (R 3.6.1)                           
##  lsei                   1.2-0       2017-10-23 [1] CRAN (R 3.6.1)                           
##  lubridate              1.7.4       2018-04-11 [1] CRAN (R 3.6.1)                           
##  magrittr               1.5         2014-11-22 [1] CRAN (R 3.6.1)                           
##  mapproj                1.2.6       2018-03-29 [1] CRAN (R 3.6.1)                           
##  maps                   3.3.0       2018-04-03 [1] CRAN (R 3.6.1)                           
##  MASS                   7.3-51.4    2019-03-31 [2] CRAN (R 3.6.1)                           
##  Matrix                 1.2-17      2019-03-22 [2] CRAN (R 3.6.1)                           
##  matrixStats          * 0.55.0      2019-09-07 [1] CRAN (R 3.6.1)                           
##  memoise                1.1.0       2017-04-21 [1] CRAN (R 3.6.1)                           
##  metap                  1.2         2019-12-08 [1] CRAN (R 3.6.1)                           
##  mime                   0.8         2019-12-19 [1] CRAN (R 3.6.1)                           
##  mnormt                 1.5-5       2016-10-15 [1] CRAN (R 3.6.1)                           
##  ModelMetrics           1.2.2       2018-11-03 [1] CRAN (R 3.6.1)                           
##  modelr                 0.1.5       2019-08-08 [1] CRAN (R 3.6.1)                           
##  moduleScoreR         * 0.0.0.9200  2020-01-05 [1] Github (milescsmith/moduleScoreR@e6db70f)
##  multcomp               1.4-11      2019-12-10 [1] CRAN (R 3.6.1)                           
##  multtest               2.42.0      2019-10-29 [1] Bioconductor                             
##  munsell                0.5.0       2018-06-12 [1] CRAN (R 3.6.1)                           
##  mutoss                 0.1-12      2017-12-04 [1] CRAN (R 3.6.1)                           
##  mvtnorm                1.0-11      2019-06-19 [1] CRAN (R 3.6.1)                           
##  nlme                   3.1-141     2019-08-01 [2] CRAN (R 3.6.1)                           
##  NMF                    0.21.0      2018-03-06 [1] CRAN (R 3.6.1)                           
##  nnet                   7.3-12      2016-02-02 [2] CRAN (R 3.6.1)                           
##  npsurv                 0.4-0       2017-10-14 [1] CRAN (R 3.6.1)                           
##  numDeriv               2016.8-1.1  2019-06-06 [1] CRAN (R 3.6.1)                           
##  oaColors               0.0.4       2015-11-30 [1] CRAN (R 3.6.1)                           
##  oompaBase              3.2.9       2019-08-24 [1] CRAN (R 3.6.1)                           
##  openssl                1.4.1       2019-07-18 [1] CRAN (R 3.6.1)                           
##  paletteer            * 1.0.0       2019-12-18 [1] CRAN (R 3.6.1)                           
##  palr                   0.1.0       2019-11-07 [1] CRAN (R 3.6.1)                           
##  pals                   1.6         2019-12-04 [1] CRAN (R 3.6.1)                           
##  parallelDist           0.2.4       2018-12-12 [1] CRAN (R 3.6.1)                           
##  pbapply                1.4-2       2019-08-31 [1] CRAN (R 3.6.1)                           
##  pcaPP                  1.9-73      2018-01-14 [1] CRAN (R 3.6.1)                           
##  pheatmap             * 1.0.12      2019-01-04 [1] CRAN (R 3.6.1)                           
##  pillar                 1.4.3       2019-12-20 [1] CRAN (R 3.6.1)                           
##  pkgconfig              2.0.3       2019-09-22 [1] CRAN (R 3.6.1)                           
##  pkgmaker               0.27        2018-05-25 [1] CRAN (R 3.6.1)                           
##  plotly               * 4.9.1       2019-11-07 [1] CRAN (R 3.6.1)                           
##  plotrix                3.7-7       2019-12-05 [1] CRAN (R 3.6.1)                           
##  plyr                   1.8.5       2019-12-10 [1] CRAN (R 3.6.1)                           
##  png                    0.1-7       2013-12-03 [1] CRAN (R 3.6.1)                           
##  polyclip               1.10-0      2019-03-14 [1] CRAN (R 3.6.1)                           
##  preprocessCore         1.48.0      2019-10-29 [1] Bioconductor                             
##  prettyunits            1.0.2       2015-07-13 [1] CRAN (R 3.6.1)                           
##  prismatic              0.2.0       2019-12-01 [1] CRAN (R 3.6.1)                           
##  prodlim                2019.11.13  2019-11-17 [1] CRAN (R 3.6.1)                           
##  progress               1.2.2       2019-05-16 [1] CRAN (R 3.6.1)                           
##  promises               1.1.0       2019-10-04 [1] CRAN (R 3.6.1)                           
##  purrr                * 0.3.3       2019-10-18 [1] CRAN (R 3.6.1)                           
##  qvalue                 2.18.0      2019-10-29 [1] Bioconductor                             
##  R.methodsS3            1.7.1       2016-02-16 [1] CRAN (R 3.6.1)                           
##  R.oo                   1.23.0      2019-11-03 [1] CRAN (R 3.6.1)                           
##  R.utils                2.9.2       2019-12-08 [1] CRAN (R 3.6.1)                           
##  R6                     2.4.1       2019-11-12 [1] CRAN (R 3.6.1)                           
##  randomForest           4.6-14      2018-03-25 [1] CRAN (R 3.6.1)                           
##  RANN                   2.6.1       2019-01-08 [1] CRAN (R 3.6.1)                           
##  rappdirs               0.3.1       2016-03-28 [1] CRAN (R 3.6.1)                           
##  RColorBrewer         * 1.1-2       2014-12-07 [1] CRAN (R 3.6.1)                           
##  Rcpp                   1.0.3       2019-11-08 [1] CRAN (R 3.6.1)                           
##  RcppAnnoy              0.0.14      2019-11-12 [1] CRAN (R 3.6.1)                           
##  RcppParallel           4.4.4       2019-09-27 [1] CRAN (R 3.6.1)                           
##  RCurl                  1.95-4.12   2019-03-04 [1] CRAN (R 3.6.1)                           
##  Rdpack                 0.11-1      2019-12-14 [1] CRAN (R 3.6.1)                           
##  readr                * 1.3.1       2018-12-21 [1] CRAN (R 3.6.1)                           
##  readxl               * 1.3.1       2019-03-13 [1] CRAN (R 3.6.1)                           
##  recipes                0.1.8       2019-12-18 [1] CRAN (R 3.6.1)                           
##  registry               0.5-1       2019-03-05 [1] CRAN (R 3.6.1)                           
##  rematch2               2.1.0       2019-07-11 [1] CRAN (R 3.6.1)                           
##  reprex                 0.3.0       2019-05-16 [1] CRAN (R 3.6.1)                           
##  reshape2               1.4.3       2017-12-11 [1] CRAN (R 3.6.1)                           
##  reticulate             1.14        2019-12-17 [1] CRAN (R 3.6.1)                           
##  rlang                * 0.4.2       2019-11-23 [1] CRAN (R 3.6.1)                           
##  rmarkdown              2.0         2019-12-12 [1] CRAN (R 3.6.1)                           
##  rngtools               1.4         2019-07-01 [1] CRAN (R 3.6.1)                           
##  robust                 0.4-18.2    2019-12-26 [1] CRAN (R 3.6.1)                           
##  robustbase             0.93-5      2019-05-12 [1] CRAN (R 3.6.1)                           
##  ROCR                   1.0-7       2015-03-26 [1] CRAN (R 3.6.1)                           
##  rpart                  4.1-15      2019-04-12 [2] CRAN (R 3.6.1)                           
##  rrcov                  1.4-9       2019-11-25 [1] CRAN (R 3.6.1)                           
##  rsample              * 0.0.5       2019-07-12 [1] CRAN (R 3.6.1)                           
##  RSQLite                2.1.5       2019-12-18 [1] CRAN (R 3.6.1)                           
##  rstudioapi             0.10        2019-03-19 [1] CRAN (R 3.6.1)                           
##  rsvd                   1.0.2       2019-07-29 [1] CRAN (R 3.6.1)                           
##  Rtsne                  0.15        2018-11-10 [1] CRAN (R 3.6.1)                           
##  rvcheck                0.1.7       2019-11-29 [1] CRAN (R 3.6.1)                           
##  rvest                  0.3.5       2019-11-08 [1] CRAN (R 3.6.1)                           
##  S4Vectors            * 0.24.1      2019-12-01 [1] Bioconductor                             
##  sandwich               2.5-1       2019-04-06 [1] CRAN (R 3.6.1)                           
##  scales               * 1.1.0       2019-11-18 [1] CRAN (R 3.6.1)                           
##  scico                  1.1.0       2018-11-20 [1] CRAN (R 3.6.1)                           
##  sctransform            0.2.1       2019-12-17 [1] CRAN (R 3.6.1)                           
##  SDMTools               1.1-221.2   2019-11-30 [1] CRAN (R 3.6.1)                           
##  sessioninfo            1.1.1       2018-11-05 [1] CRAN (R 3.6.1)                           
##  Seurat               * 3.1.2       2020-01-05 [1] Github (satijalab/Seurat@49a1be0)        
##  shiny                  1.4.0       2019-10-10 [1] CRAN (R 3.6.1)                           
##  sn                     1.5-4       2019-05-14 [1] CRAN (R 3.6.1)                           
##  storr                  1.2.1       2018-10-18 [1] CRAN (R 3.6.1)                           
##  stringi                1.4.3       2019-03-12 [1] CRAN (R 3.6.1)                           
##  stringr              * 1.4.0       2019-02-10 [1] CRAN (R 3.6.1)                           
##  SummarizedExperiment * 1.16.1      2020-01-05 [1] bioc_git2r (@1004fc2)                    
##  survival               3.1-6       2019-11-06 [2] CRAN (R 3.6.1)                           
##  TFisher                0.2.0       2018-03-21 [1] CRAN (R 3.6.1)                           
##  TH.data                1.0-10      2019-01-21 [1] CRAN (R 3.6.1)                           
##  tibble               * 2.1.3       2019-06-06 [1] CRAN (R 3.6.1)                           
##  tidygraph              1.1.2       2019-02-18 [1] CRAN (R 3.6.1)                           
##  tidyr                * 1.0.0.9000  2020-01-05 [1] Github (tidyverse/tidyr@885d1af)         
##  tidyselect           * 0.2.5       2018-10-11 [1] CRAN (R 3.6.1)                           
##  tidyverse            * 1.3.0       2019-11-21 [1] CRAN (R 3.6.1)                           
##  timeDate               3043.102    2018-02-21 [1] CRAN (R 3.6.1)                           
##  triebeard              0.3.0       2016-08-04 [1] CRAN (R 3.6.1)                           
##  tsne                   0.1-3       2016-07-15 [1] CRAN (R 3.6.1)                           
##  tweenr                 1.0.1       2018-12-14 [1] CRAN (R 3.6.1)                           
##  tximport             * 1.14.0      2019-10-29 [1] Bioconductor                             
##  txtq                   0.2.0       2019-10-15 [1] CRAN (R 3.6.1)                           
##  urltools               1.7.3       2019-04-14 [1] CRAN (R 3.6.1)                           
##  uwot                   0.1.5       2019-12-04 [1] CRAN (R 3.6.1)                           
##  vctrs                  0.2.99.9001 2020-01-05 [1] Github (r-lib/vctrs@4fadaa0)             
##  viridis              * 0.5.1       2018-03-29 [1] CRAN (R 3.6.1)                           
##  viridisLite          * 0.3.0       2018-02-01 [1] CRAN (R 3.6.1)                           
##  webshot                0.5.2       2019-11-22 [1] CRAN (R 3.6.1)                           
##  WGCNA                * 1.68        2019-05-23 [1] CRAN (R 3.6.1)                           
##  withr                  2.1.2       2018-03-15 [1] CRAN (R 3.6.1)                           
##  xfun                   0.11        2019-11-12 [1] CRAN (R 3.6.1)                           
##  XML                    3.98-1.20   2019-06-06 [1] CRAN (R 3.6.1)                           
##  xml2                   1.2.2       2019-08-09 [1] CRAN (R 3.6.1)                           
##  xtable                 1.8-4       2019-04-21 [1] CRAN (R 3.6.1)                           
##  XVector                0.26.0      2019-10-29 [1] Bioconductor                             
##  yaml                   2.2.0       2018-07-25 [1] CRAN (R 3.6.1)                           
##  zip                    2.0.4       2019-09-01 [1] CRAN (R 3.6.1)                           
##  zlibbioc               1.32.0      2019-10-29 [1] Bioconductor                             
##  zoo                    1.8-6       2019-05-28 [1] CRAN (R 3.6.1)                           
## 
## [1] /usr/local/lib/R/site-library
## [2] /usr/local/lib/R/library